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Faculty Detail    
Name XU FENG
 
Campus Address VH G019 Zip 0019
Phone
E-mail  xfeng@uabmc.edu
Other websites
     

Education
Undergraduate  Fudan University, Shanghai, China    1987  Bachelor of Science  
Graduate  University of Vermont, Burlington, VT    1994  Ph.D. in Zoology/Molecular Biology 
Fellowship  Washington University School of Medicine, St. Louis, MO    1999  Bone Biology 


Faculty Appointment(s)
Appointment Type Department Division Rank
Center  Biomedical Engineering  Biomatrix Eng Regen Med (BERM) Ctr Professor
Center  Pathology   Cell Adhesion & Matrix Research Center Professor
Center  Center for Biophysical Sciences/Engineering  Center for Biophysical Sciences/Engineering Professor
Center  Comp Arthritis, MSK, Bone & Autoimmunity Ctr  Comp Arthritis, MSK, Bone & Autoimmunity Ctr Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor
Center  Integrative Center for Aging Research  Integrative Center for Aging Research Professor
Primary  Pathology   Molecular & Cellular Pathology Professor

Graduate Biomedical Sciences Affiliations
Cancer Biology 
Immunology 
Medical Scientist Training Program 
Molecular and Cellular Pathology Program 
Pathobiology and Molecular Medicine 

Biographical Sketch 
Dr. Feng received his B.S. degree in 1987 from Fudan University in China and his Ph.D. in Zoology/Molecular Biology from the University of Vermont in 1994 (Advisor, Dr. George Happ). He then pursued his postdoctoral research training in the laboratory of Dr Steven Teitelbaum in Department of Pathology at Washington University School of Medicine in St. Louis. In 2000, Dr. Feng joined Department of Pathology at the University of Alabama at Birmingham. He received National Research Service Award from National Institutes of Health (1997-1999) and was also a recipient of John Haddad Young Investigator Award from Advances in Mineral Metabolism (AIMM) and the American Society for Bone and Mineral Research (ASBMR) in 2000.

Society Memberships
Organization Name Position Held Org Link
American Society for Biochemistry and Molecular Biology (ASBMB)    http://www.asbmb.org/ 
American Society for Bone and Mineral Research (ASBMR)    http://www.asbmr.org/Default.aspx 



Research/Clinical Interest
Title
The RANKL/RANK/OPG System in Health and Disease
Description
Our laboratory uses molecular and cell biology techniques as well as mouse models (knockout and knockin) to delineate the signaling mechanisms by which the RANKL/RANK/OPG system regulates cell differentiation and function. Currently, we have the following research focuses: (1) RANK signaling mechanism in osteoclast differentiation and function. RANKL is a key factor regulating the formation and function of osteoclasts, our body’s sole bone-resorbing cells, which play a pivotal role in skeletal development and adult skeletal maintenance (bone remodeling). Moreover, the RANKL/RANK/OPG system is also implicated in the pathogenesis of various diseases including postmenopausal osteoporosis, bone erosion in rheumatoid arthritis, periodontal bone loss, and tumor (breast and prostate) skeletal metastasis. Our long-term goals are a) to elucidate the signaling mechanism by which the RANKL/RANK/OPG system regulates osteoclast formation and function and b) to delineate the molecular and cellular mechanisms underlying the role of the RANKL/RANK/OPG system in the various bone diseases. (2) The molecular mechanism by which the RANKL/RANK/OPG system regulates mammary gland development and promotes breast cancer development and metastasis. While the crucial role of the RANKL/RANK/OPG system in mammary gland development has been well established, the signaling mechanism controlling RANKL-mediated mammary gland development has not been fully understood. The objectives of this research focus are a) to delineate novel RANK signaling pathways involved in mammary gland development and b) to better understand the molecular mechanism by which the RANKL/RANK/OPG system promotes breast cancer initiation and progression. (3) Drug discovery/translational research. Our work on RANK signaling mechanism in osteoclast biology has led to identification of several RANK cytoplasmic motifs/signaling pathways that play important functional roles in osteoclast formation and function. The potency and selectivity of these RANK motif-mediated signaling pathways in osteoclast biology have convinced us to expand our research program into the translational research. We have developed cell-based assay systems for identifying compounds targeting these RANK motif-mediated signaling pathways through high throughput screening (HTS). The goal of this translational research is to develop new antiresorptive drugs targeting the RANKL/RANK/OPG system.

Selected Publications 
Publication PUBMEDID
Ashley JW, Shi Z, Zhao H, Li X, Kesterson RA, Feng X (2011) Genetic ablation of CD68 results in mice with increased bone and dysfunctional osteoclasts. PLoS One. 6(10):e25838.   21991369  
Cheng J, Liu J, Shi Z, Jules J, Xu D, Luo S, Wei S, Feng X (2012) Molecular mechanisms of the biphasic effects of interferon-γ on osteoclastogenesis. J Interferon Cytokine Res. 32(1):34-45.   22142221 
Jules J, Zhang P, Ashley JW, Wei S, Shi Z, Liu J, Michalek SM, Feng X (2012) Molecular basis of requirement of receptor activator of nuclear factor κB signaling for interleukin 1-mediated osteoclastogenesis. J Biol Chem. 287(19):15728-38.   22416138  
MohanKumar K, Kaza N, Jagadeeswaran R, Garzon SA, Bansal A, Kurundkar AR, Namachivayam K, Remon JI, Bandepalli CR, Feng X, Weitkamp JH, Maheshwari A (2012) Gut mucosal injury in neonates is marked by macrophage infiltration in contrast to pleomorphic infiltrates in adult: evidence from an animal model. Am J Physiol Gastrointest Liver Physiol. 303(1):G93-102.   22538401  
Izawa T, Zou W, Chappel JC, Ashley JW, Feng X, Teitelbaum SL (2012) c-Src links a RANK/αvβ3 integrin complex to the osteoclast cytoskeleton. Mol Cell Biol. 32(14):2943-53.  22615494  
Sawant A, Deshane J, Jules J, Lee CM, Harris BA, Feng X, Ponnazhagan S (2013) Myeloid-derived suppressor cells function as novel osteoclast progenitors enhancing bone loss in breast cancer. Cancer Res. 73(2):672-82.   23243021  
McCoy EM, Hong H, Pruitt HC, Feng X (2013) IL-11 produced by breast cancer cells augments osteoclastogenesis by sustaining the pool of osteoclast progenitor cells. BMC Cancer. 13:16.   23311882 
Cody JJ, Rivera AA, Lyons GR, Yang SW, Wang M, Ashley JW, Meleth S, Feng X, Siegal GP, Douglas JT (2013) Expression of osteoprotegerin from a replicating adenovirus inhibits the progression of prostate cancer bone metastases in a murine model. Lab Invest. 93(3):268-78.   23358109 
Xia WF, Tang FL, Xiong L, Xiong S, Jung JU, Lee DH, Li XS, Feng X, Mei L, Xiong WC (2013) Vps35 loss promotes hyperresorptive osteoclastogenesis and osteoporosis via sustained RANKL signaling. J Cell Biol. 200(6):821-37.   23509071 
Hong H, Shi Z, Qiao P, Li H, McCoy EM, Mao P, Xu H, Feng X, Wang S (2013) Interleukin-3 plays dual roles in osteoclastogenesis by promoting the development of osteoclast progenitors but inhibiting the osteoclastogenic process. Biochem Biophys Res Commun. 440(4):545-50.  24103757 
Chu GC, Zhau HE, Wang R, Rogatko A, Feng X, Zayzafoon M, Liu Y, Farach-Carson MC, You S, Kim J, Freeman MR, Chung L (2014) RANK- and c-Met-mediated signal network promotes prostate cancer metastatic colonization. Endocr Relat Cancer. 21: 311-26  24478054 
Jules J and Feng X (2014) In vitro investigation of the roles of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1 in murine osteoclastogenesis. Methods Mol Biol. 1155:109-23.  24788177 
Zhao D, Shi Z, Warriner AH, Qiao P, Hong H, Wang Y, Feng X. Molecular mechanism of thiazolidinedione-mediated inhibitory effects on osteoclastogenesis. PLoS One. 2014 Jul 17;9(7):e102706.  25032991 
Feng X and Teitelbaum SL (2013) Osteoclasts: New Insights. Bone Research. 1 (1) 11-26  26273491 
Jules J, Wang S, Shi Z, Liu J, Wei S, Feng X (2015) The IVVY Motif and Tumor Necrosis Factor Receptor-associated Factor (TRAF) Sites in the Cytoplasmic Domain of the Receptor Activator of Nuclear Factor κB (RANK) Cooperate to Induce Osteoclastogenesis. J Biol Chem. 290(39):23738-50.  26276390 
Chen Z, Su L, Xu Q, Katz J, Michalek SM, Fan M, Feng X, Zhang P (2015) IL-1R/TLR2 through MyD88 divergently modulates osteoclastogenesis through regulation of nuclear factor of activated T cells c1 (NFATc1) and B lymphocyte-induced maturation protein-1 (Blimp1). J Biol Chem. 290(50):30163-74.  26483549 
Jules J, Chen W, Feng X, Li YP. (2016) CCAAT/enhancer binding protein α (C/EBPα) is important for osteoclast differentiation and activity J Biol Chem. 291(31):16390-403  27129246 
Jules J, Chen W, Feng X, Li YP (2018) C/EBPα is regulated by the RANK cytoplasmic IVVY535-538 motif and stimulates osteoclastogenesis more strongly than c-Fos. J Biol Chem. 293(4):1480-1492.   29122885  
Li Y, Shi Z, Jules J, Chen S, Kesterson RA, Zhao D, Zhang P, Feng X (2019) Specific RANK cytoplasmic motifs drive osteoclastogenesis. J Bone Miner Res. 34:1938-1951  31173390 
Cai X, Li Z, Zhao Y, Katz J, Michalek SM, Feng X, Li Y, Zhang P (2020) Enhanced dual function of osteoclast precursors following calvarial Porphyromonas gingivalis infection. J Periodontal Res 55(3):410-425  31944305 
Zhao Y, Li Z, Su L, Ballesteros-Tato A, Katz J, Michalek S, Feng X, Zhang P (2020) Characterization and regulation of osteoclast precursors following chronic Porphyromonas gingivalis infection Journal of Leukocyte Biology, 108(4):1037-1050  33463750 
Paesen GC, Feng X, Happ GM (1996) Structure of a D-protein gene and amino-acid sequences of the highly repetitive D-proteins secreted by the accessory glands of the mealworm beetle. Biochim Biophys Acta. 1293(2):171-6.  8620026 
Cao X, Teitelbaum SL, Zhu HJ, Zhang L, Feng X, Ross FP (1996) Competition for a unique response element mediates retinoic acid inhibition of vitamin D3-stimulated transcription. J Biol Chem. 271(34):20650-4.  8702813 
Feng X, Happ GM (1996) Isolation and sequencing of the gene encoding Sp23, a structural protein of spermatophore of the mealworm beetle, Tenebrio molitor. Gene. 179(2):257-62.  8972909 
Feng X, Teitelbaum SL, Quiroz ME, Towler DA, Ross FP (1999) Cloning of the murine beta5 integrin subunit promoter. Identification of a novel sequence mediating granulocyte-macrophage colony-stimulating factor-dependent repression of beta5 integrin gene transcription. J Biol Chem. 274(3):1366-74.  9880508 

Keywords
RANKL, RANK, OPG, Cell Differentiation, Cell Signaling, Osteoclast, Mammary Gland, Breast Cancer